The regulated assembly of actin is critical for cell motility, maintenance of shape and adhesion. A variety of extracellular stimuli induce reorganization of the actin cytoskeleton, but the detailed mechanisms by which extracellular stimuli lead to actin reorganization remain unclear. The long-term objective of this proposal is to define the molecular basis of regulated actin assembly in cells; in this proposal, we specifically address the role of actin filament fragmentation in stimulus induced shape change. Actin filament severing and capping proteins have been postulated to be key regulators of actin dynamics in the cell by fragmenting filaments and increasing the number of filament ends. In vitro, an increase in the number of regulated high affinity ends increases the conversion of monomer to filament, while increasing the number of low affinity ends increases the conversion of filaments to monomer. Using fluorescent analogs and specific probes we will test the hypothesis that actin filament severing is a consequence of stimuli which induce specific types of shape change and motility.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM057256-02
Application #
6151210
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Program Officer
Deatherage, James F
Project Start
1999-02-01
Project End
2004-01-31
Budget Start
2000-02-01
Budget End
2001-01-31
Support Year
2
Fiscal Year
2000
Total Cost
$219,353
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02115
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